Limb and patient outcomes in people with diabetic foot complications including diabetic foot ulcer (DFU) provided virtual triage and personalized video consultations during COVID-19 pandemic are not ...known.
Patients with foot complications attending the diabetic foot clinic prior to lockdown who sought teleconsultations during COVID-19 lockdown underwent virtual triage to include clinical history, visual inspection of feet, domiciliary wound care (community nurse assisted dressings) and offloading instructions. The subsequent ulcer, limb and mortality outcomes during the following 24 weeks of COVID-19 lockdown (April-September 2020, group 1) were assessed and compared with those who attended foot clinic during the same period in 2019 (April-September, group 2).
Group 1 included 561 participants with foot complications provided with teleconsultations, median age 57 (51 to 63) years and diabetes duration of 10 (5 to 16) years. Twelve patients with severe DFU were excluded and 549 patients 357 (65%) neuropathic foot, 104 (18.9%) ischemic foot and 88 (16%) chronic Charcot foot with deformities were evaluated. There were 227 (41.3%) participants with active DFU at start of lockdown, 32 (5.8%) with new onset ulcer during lockdown (47.1%) and 290 patients without ulcers. Group 2 included 650 participants; active foot ulcer was present in 366 patients. Wound closed or reduced in area in 78.4% of participants of group 1 compared to 76.0% (p = 0.318) in group 2. Fourteen (5.4%) patients required amputations 3 major and 11 minor in group 1 during the study period compared to 6.8% in group 2 (p = 0.191). Twenty-one (3.8%) and 28 (4.3%) patients died (p = 0.532) during 24 weeks of follow up in group 1 and 2, respectively.
Targeted foot-care service through virtual triage and teleconsultations during COVID-19 pandemic for people with foot complications have similar ulcer and limb outcomes compared to face-to-face foot care delivery.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Inoperable and metastatic pheochromocytomas and paragangliomas (PPGLs) present a therapeutic challenge with current treatment options being limited to radiolabelled ...meta‐iodo‐benzyl‐guanidine (MIBG) and systemic chemotherapy. Peptide receptor radionuclide therapy (PRRT) seems to be a promising option for these patients with few studies reporting favourable response. This systematic review was conducted to evaluate the efficacy and safety of PRRT in patients with advanced PPGLs.
Methods
This review followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines. Searches in PubMed, Scopus and Embase were made using relevant keywords and articles up to May 2019 were included. Data on efficacy and toxicity were extracted from the individual articles, and pooled estimates were generated using meta‐analysis.
Results
Twelve articles consisting of 201 patients with advanced PPGLs were included. Overall, treatment with PRRT achieved an objective response rate of 25% (95% CI: 19%‐32%) and a disease control rate of 84% (95% CI: 77%‐89%). Clinical and biochemical responses were seen in 61% and 64% of the patients, respectively. Among the PRRTs, similar tumour response rates were noted for 90Y—yttrium‐ and 177Lu—lutetium‐based agents. Treatment‐related adverse effects were minimal with grade 3/4 neutropenia, thrombocytopenia, lymphopenia and nephrotoxicity observed in 3%, 9%, 11% and 4% of the patients, respectively. Treatment discontinuation was noted in five out of 102 patients.
Conclusions
Peptide receptor radionuclide therapy is a safe and efficacious treatment option for advanced PPGLs and may be considered a viable alternative to chemotherapy and I‐131 MIBG.
Purpose
Both laparoscopic sleeve gastrectomy (LSG) and liraglutide cause a significant weight loss. We evaluated the effect of liraglutide in comparison with placebo on total weight loss (TWL) and ...excess body weight loss (EWL) and when added in initial weight loss period after LSG in obese individuals.
Material and Methods
Participants with BMI > 30 kg/m
2
undergoing LSG were randomised to receive either liraglutide (subcutaneous) in increasing does of 0.6 mg/day until maximum tolerated dose of 3.0 mg (L-L group) or placebo (L-P group) from 6 weeks post-operative until 6 months. Weight, BMI, %TWL, %EWL, HbA1c, fasting plasma glucose, HOMA-IR, resolution of type 2 diabetes mellitus, hypertension, dyslipidaemia, sleep apnea and quality of life were evaluated. Primary end point was %TWL and % EWL at post-operative 6 months.
Results
Thirty participants underwent LSG, and 23 were randomised to receive liraglutide (
n
= 12) or placebo (
n
= 11).The mean dose of liraglutide in L-L group was 1.41 ± 0.49 mg/day. Patients in L-L group had %TWL of 28.2 ± 5.7 and %EWL of 58.7 ± 14.3 as compared with 23.2 ± 6.2 (
p
= 0.116) and 44.5 ± 8.6 (
p
= 0.043) in L-P group at 24 weeks, respectively. BMI decreased by 11.7 ± 3.5 in L-L group compared with 9.5 ± 4.0 in L-P group (
p
= 0.287). All patients with diabetes or pre-diabetes had resolution of dysglycemia in the L-L group as compared with 50% in L-P group. However, there was no significant difference in resolution of other obesity-related comorbidities between two groups at 24-week follow-up.
Conclusion
Liraglutide added early after LSG significantly augments weight loss from LSG in obese individuals.
Trial Registration
The study protocol was registered at clinical
trials.gov.in
with NCT: 04325581.
Hyperglycemia-mediated oxidative stress impedes cell-reparative process like autophagy, which has been implicated in impairment of β-cell function in type 2 diabetes mellitus (T2DM). However, the ...role of mitophagy (selective mitochondrial autophagy) in progression of hyperglycemia remains elusive. This study aimed to assess the impact of increasing severity of hyperglycemia on mitochondrial stress and mitophagy.
A case-control study included healthy controls, subjects with prediabetes, newly diagnosed T2DM (NDT2DM) and advanced duration of T2DM (ADT2DM) (
= 20 each). Mitochondrial stress indices, transcriptional and translational expression of mitophagy markers (
, and
) and transmission electron microscopic (TEM) studies were performed in peripheral blood mononuclear cells.
With mild hyperglycemia in subjects with prediabetes, to moderate to severe hyperglycemia in NDT2DM and ADT2DM, a progressive rise in mitochondrial oxidative stress was observed. Prediabetic subjects exhibited significantly increased expression of mitophagy-related markers and showed a positive association with HOMA-β, whereas, patients with NDT2DM and ADT2DM demonstrated decreased expression, with a greater decline in ADT2DM subjects. TEM studies revealed significantly reduced number of distorted mitochondria in prediabetics, as compared to the T2DM patients. In addition, receiver operating characteristic analysis showed HbA
> 7% (53 mmol/mol) was associated with attenuated mitophagy.
Increasing hyperglycemia is associated with progressive rise in oxidative stress and altered mitochondrial morphology. Sustenance of mitophagy at HbA
< 7% (53 mmol/mol) strengthens the rationale of achieving HbA
below this cutoff for good glycemic control. An "adaptive" increase in mitophagy may delay progression to T2DM by preserving the β-cell function in subjects with prediabetes.
Background and aims
COVID-19 is likely to affect the lives of individuals with type 2 diabetes. However, the effect of COVID-19 lockdown on physical activity and glycemic control in such individuals ...is not known. We studied the physical activity and glycemic control during lockdown in comparison to pre-lockdown parameters in individuals with long-standing type 2 diabetes.
Methods
This prospective, observational study includes 2240 people with T2DM regularly attending diabetes clinic prior to lockdown. Glycemic record, HbA1c, and physical activity assessed with Global Physical Activity Questionnaire (GPAQ) as metabolic equivalents (MetS min/week) were obtained during lockdown (minimum duration of 3 months).
Results
A total of 422 out of 750 participants (nest) responded. The median (IQR) for age was 58 (52 to 64) years, duration of diabetes 11 (6 to 16) years, prevalent foot complications in 59.7%, and atherosclerotic cardiovascular disease in 21.3% of participants. There was a decrease in HbA1c from 7.8% (6.9 to 9.4) prior lockdown to 7.4% (6.6 to8.7) during lockdown ΔHbA1c − 0.41 ± 0.27% (
p
= 0.005) and postprandial blood glucose 200.0 mg/dl (152.0 to 252.0) to 158.0 (140.0 to 200.0) mg/dl (
p
< 0.001). The physical activity increased during lockdown from a GPAQ score 140 (0.0 to 1260) MetS to 840 (0.0 to 1680) MetS (
p
= 0.014). The improvement of glycemic control was observed in either gender and independent of the presence of foot complications or increase in physical activity.
Conclusions
There is an overall improvement of glycemic control during COVID-19 lockdown independent of increase in physical activity in people with long duration of diabetes.
No pharmacotherapeutic agents are yet recommended for active CN though many anti-resorptive agents have been studied. We conducted a systematic review and meta-analysis of the randomized ...placebo-controlled trials (RCTs) evaluating the time to remission of active CN with anti-resorptive or antiinflammatory drugs. RCTs published in PubMed, EMBASE, SCOPUS and Cochrane Library from January 1994 to December 2019 were accessed. We reviewed studies and extracted information on study design, participants’ characteristics, time to remission, bone turnover markers, bone mineral content (BMC) and temperature difference between feet. Five RCTs out of 588 total identified records were included. Standardized mean differences (SMD) between groups with 95% CI are summarized. Pharmacotherapy nonsignificantly increased time to remission SMD 0.52 weeks (− 0.71, 1.75), p = 0.402; I2 = 88.6% as compared to TCC alone. The pooled median time to remission with the intervention was 18.5 weeks (11.2, 28.1) compared to 16.8 weeks (8.7, 27.7) with TCC. A nonsignificant increase in BMC SMD 3.39% (− 0.78, 7.56), p = 0.109; I2 = 96.7%, a decrease in foot temperature SMD − 0.42 °C (− 0.78, − 0.07), p = 0.020; I2 = 0% and alkaline phosphatase SMD = −2.51% (− 3.24, − 1.77), p < 0.001; I2 = 0% was observed with intervention. Limited evidence from available studies does not support the role of anti-resorptive or anti-inflammatory drugs for earlier remission when added to offloading with total contact cast for active CN of the foot.
Inactivating germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are linked to pituitary adenoma predisposition. Here, we present the youngest known patient with ...AIP-related pituitary adenoma.
The patient presented at the age of 4 years with pituitary apoplexy and left ptosis with severe visual loss following a 1-year history of abdominal pain, headaches, and rapid growth. His IGF-1 level was 5× the upper limit of normal, and his random GH level was 1200 ng/mL. MRI showed a 43 × 24 × 35‒mm adenoma with suprasellar extension invading the left cavernous sinus (Knosp grade 4). After transsphenoidal surgery, histology showed a grade 2A sparsely granulated somatotropinoma with negative O6-methylguanine-DNA methyltransferase and positive vascular endothelial growth factor staining. Genetic testing identified a heterozygous germline nonsense AIP mutation (p.Arg81Ter). Exome sequencing of the tumor revealed that it had lost the entire maternal chromosome-11, rendering it hemizygous for chromosome-11 and therefore lacking functional copies of AIP in the tumor. He was started on octreotide, but because the tumor rapidly regrew and IGF-1 levels were unchanged, temozolomide was initiated, and intensity-modulated radiotherapy was administered 5 months after surgery. Two months later, bevacizumab was added, resulting in excellent tumor response. Although these treatments stabilized tumor growth over 4 years, IGF-1 was normalized only after pegvisomant treatment, although access to this medication was intermittent. At 3.5 years of follow-up, gamma knife treatment was administered, and pegvisomant dose increase was indicated.
Multimodal treatment with surgery, long-acting octreotide, radiotherapy, temozolomide, bevacizumab, and pegvisomant can control genetically driven, aggressive, childhood-onset somatotropinomas.
This systematic review aimed to ascertain the diagnostic accuracy (sensitivity and specificity) of screening tests for early detection of type 2 diabetes and prediabetes in previously undiagnosed ...adults.
This systematic review included published studies that included one or more index tests (random and fasting tests, HbA1c) for glucose detection, with 75-gram Oral Glucose Tolerance Test (or 2-hour post load glucose) as a reference standard (PROSPERO ID CRD42018102477). Seven databases were searched electronically (from their inception up to March 9, 2020) accompanied with bibliographic and website searches. Records were manually screened and full text were selected based on inclusion and exclusion criteria. Subsequently, data extraction was done using standardized form and quality assessment of studies using QUADAS-2 tool. Meta-analysis was done using bivariate model using Stata 14.0. Optimal cut offs in terms of sensitivity and specificity for the tests were analysed using R software.
Of 7,151 records assessed by title and abstract, a total of 37 peer reviewed articles were included in this systematic review. The pooled sensitivity, specificity, positive (LR+) and negative likelihood ratio (LR-) for diagnosing diabetes with HbA1c (6.5%; venous sample; n = 17 studies) were 50% (95% CI: 42-59%), 97.3% (95% CI: 95.3-98.4), 18.32 (95% CI: 11.06-30.53) and 0.51 (95% CI: 0.43-0.60), respectively. However, the optimal cut-off for diagnosing diabetes in previously undiagnosed adults with HbA1c was estimated as 6.03% with pooled sensitivity of 73.9% (95% CI: 68-79.1%) and specificity of 87.2% (95% CI: 82-91%). The optimal cut-off for Fasting Plasma Glucose (FPG) was estimated as 104 milligram/dL (mg/dL) with a sensitivity of 82.3% (95% CI: 74.6-88.1%) and specificity of 89.4% (95% CI: 85.2-92.5%).
Our findings suggest that at present recommended threshold of 6.5%, HbA1c is more specific and less sensitive in diagnosing the newly detected diabetes in undiagnosed population from community settings. Lowering of thresholds for HbA1c and FPG to 6.03% and 104 mg/dL for early detection in previously undiagnosed persons for screening purposes may be considered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To study the pattern and prevalence of dyslipidemia in a large representative sample of four selected regions in India.
Phase I of the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) ...study was conducted in a representative population of three states of India Tamil Nadu, Maharashtra and Jharkhand and one Union Territory Chandigarh, and covered a population of 213 million people using stratified multistage sampling design to recruit individuals ≥20 years of age. All the study subjects (n = 16,607) underwent anthropometric measurements and oral glucose tolerance tests were done using capillary blood (except in self-reported diabetes). In addition, in every 5th subject (n = 2042), a fasting venous sample was collected and assayed for lipids. Dyslipidemia was diagnosed using National Cholesterol Education Programme (NCEP) guidelines.
Of the subjects studied, 13.9% had hypercholesterolemia, 29.5% had hypertriglyceridemia, 72.3% had low HDL-C, 11.8% had high LDL-C levels and 79% had abnormalities in one of the lipid parameters. Regional disparity exists with the highest rates of hypercholesterolemia observed in Tamilnadu (18.3%), highest rates of hypertriglyceridemia in Chandigarh (38.6%), highest rates of low HDL-C in Jharkhand (76.8%) and highest rates of high LDL-C in Tamilnadu (15.8%). Except for low HDL-C and in the state of Maharashtra, in all other states, urban residents had the highest prevalence of lipid abnormalities compared to rural residents. Low HDL-C was the most common lipid abnormality (72.3%) in all the four regions studied; in 44.9% of subjects, it was present as an isolated abnormality. Common significant risk factors for dyslipidemia included obesity, diabetes, and dysglycemia.
The prevalence of dyslipidemia is very high in India, which calls for urgent lifestyle intervention strategies to prevent and manage this important cardiovascular risk factor.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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